Dr. Bhavik Miyani, Resident Doctor in Department of Oral & Maxillofacial Surgery, NPDCH, Visnagar.

1. #7th Journal Club Presentation
Presented By,
Dr. Bhavik Miyani
2nd Year PG,
Department of OMFS.
Guided By,
Dr. Anil Managutti,
Dr. Shailesh Menat,
Dr. Rushit Patel,
Dr. Jigar Patel.

2. {
A novel approach to the management of a
central giant cell granuloma with
denosumab: A case report and review of
current treatments
AUTHORS: Benjamin Gupta ,
Norman Stanton,
Hedley Coleman,
Chris White,
Jasvir Singh
JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY
43 (2015) 1127-1132

3. Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

4.  Present report describes a case of CGCG of the
mandible that were treated effectively with
subcutaneous denosumab.
 Represents a viable alternative or adjunctive
procedure
 Eliminates or decreases the extent of surgical
intervention, hence morbidity
 Future prospective studies required to evaluate
long-term effects and possible adverse side
effects.
SUMMARY

5.  To project Denosumab as a novel therapeutic
agent in treating central giant cell granuloma
 Evaluating merits, demerits, mechanism of
action
 Reviewing other medicinal treatment modalities
for CGCG
AIMS

6.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

7.  Central giant cell granuloma (CGCG) of the
jaws was first documented as “giant-cell
reparative granuloma” by Jaffe1 in 1953
 Although CGCGs of the jaws have no
significant malignant potential, they can be
locally aggressive, with a high recurrence
rate, and produce cortical expansion,
displacement of teeth, root resorption, and
sensory alteration.
INTRODUCTION

8.  The most frequent treatment of CGCG is surgical
curettage, which results in a recurrence rate of 11
to 49%
 Surgical resection with 0.5-cm margins is much
more effective, resulting in a recurrence rate of
6%
 However, complete surgical resection may
extensively compromise esthetics and function in
some cases

9.  The overall recurrence rate was found to be
26.3% in the largest review of CGCG in the
literature.
 The highest rates of recurrence are seen in
tumors exhibiting aggressive clinical behavior,
producing pain, paresthesia, and root resorption

10.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

11.  A 33-year-old female with pain in the region of
tooth 46
 Clinical examination revealed mobile teeth 45, 47
with firm expansive swelling in the right body of
mandible
 No associated lymphadenopathy or sensory
disturbance
MATERIALS AND METHODS

12.  Treatment initiated with weekly intralesional
triamcinolone injections of 20mg for 6 weeks
 No response
 Dosage increased to 40mg and treatment
continued for next weeks
 Still no improvement

13.  Subcutaneous calcitonin initiated
 100mg daily injections were given
 Intranasal sprays can also be used
 No satisfactory results

14.  Denosumab initiated
 120mg subcutaneous injections
 Initial loading dose on 8th and 15th day
 Followed by monthly injections for 6 months
 Followed by two 6 monthly injections

15.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

16.  Early clinical response observed with resolution
of patient symptoms within 10 days
 Follow-up radiographs at 6 months
demonstrated ossification of the lesion
 Patient was reluctant to undergo further
mandibular recontouring surgery
 A follow up biopsy performed 18 months later
demonstrated no evidence of residual CGCG
RESULTS

17. Pre-treatment Post-treatment

18.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

19. DISCUSSION
DENOSUMAB
Human monoclonal antibody
Binds to receptor activator of nuclear factor- kB
ligand
(key factor in production and maturation of
giant cells and osteoclasts)

20.  First published study by Thomas et al in 2010
 Involved 37 patients of Giant cell tumor of
bone
 The primary endpoint was tumour response,
defined as elimination of at least 90% of giant
cells or no radiological progression of the
target lesion up to week 25

21.  Important consideration is the risk of ORN
 There have been three large double blind, Phase III
randomized trials that have compared zoledronic
acid with denosumab.
 The incidence of osteonecrosis of the jaws was
similar for both preparations (1.3% vs. 1.8%)
respectively with a total of 89 cases out of 5677
patients.

22.  Malmquist & Schow9 have described 2
patients with evidence of decreased lesion
size and new bone formation
 Schreuder et al. have also published a report
of a maxillary CGCG treated successfully with
denosumab

23. INTRALESIONAL STEROIDS
Inhibit the production Induce apoptosis of
of bone resorption osteoclasts
mediating lysosomal
proteases by giant cells.

24.  first reported for the treatment of CGCG in 1988
by Jacoway
 Steroids may also induce the apoptosis of
osteoclast-like cells
 It has been estimated that 65% of CGCG lesions
completely resolve with corticosteroids, with the
remainder either unresponsive to therapy or
recurring with more aggressive behaviour

25. INTERFERONS
suppression of fibroblast growth factors,
which may slow angiogenesis in tumors
CALCITONIN

26.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

34.  Aims
 Introduction
 Material and methods
 Results
 Discussion
 Review studies
 References
Contents

35. 1) H.L. JaffeGiant-cell reparative granuloma, traumatic bone cyst, and fibrous
(fibro-osseous) dysplasia of the jawbones Oral Surg, 6 (1953), p. 159
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radiologic, and histopathologic study Oral Surg Oral Med Oral Pathol, 75 (1993),
p. 199
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giant-cell lesions of the jaw Oral Surg Oral Med Oral Pathol Oral Radiol Endod,
99 (2005), p. 464
4)J. de Lange, H.P. van den Akker, H. van den Berg Central giant cell granuloma
of the jaw: A review of the literature with emphasis on therapy options
5) J. de Lange, H.P. van den Akker, H. Klip Incidence and disease-free survival
after surgical therapy of central giant-cell granulomas of the jaw in The
Netherlands: 1990-1995

36. 6) A.B. Bataineh, T. Al-Khateeb, M.A. Rawashdeh The surgical treatment of central
giant cell granuloma of the mandible J Oral Maxillofac Surg, 60 (2002), p. 756
7) M.A. Rawashdeh, A.B. Bataineh, T. Al-Khateeb Long-term clinical and
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the maxilla Int J Oral Maxillofac Surg, 35 (2006), p. 60
8) A. Lipton, K. Fizazi, A.T. Stopeck, D.H. Henry, J.E. Brown, D.A. Yardley, et al.
Superiority of denosumab to zoledronic acid for prevention of skeletal-related
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48 (16) (2012), pp. 3082–3092
9) M. Malmquist, S. Schow Treatment of Central giant cell granuloma with
denosumab therapy in two patients J Oral Maxillofac Surg, 71 (2013), p. e75
10) W.H. Schreuder, A.W. Coumou, P.A. Kessler, J. de Lange Alternative
pharmacologic therapy for aggressive Central giant cell granuloma: denosumab
J Oral Maxillofac Surg, 72 (2014), pp. 1301–1309

37. 11) J. Jacoway, F. Howell, B. Terry Central giant cell granuloma: an alternative to
surgical therapy Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 66 (1988), p.
572
12) R. Carlos, H.O. Sedano Intralesional corticosteroids as an alternative
treatment for central giant cell granuloma Oral Surg Oral Med Oral Pathol Oral
Radiol Endod, 93 (2) (2002), pp. 161–166
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of a central giant cell granuloma with intralesional corticosteroid Br J Oral
Maxillofac Surg, 43 (1) (2005), pp. 74–76
14) R.E. Marx, D. Stern Oral and maxillofacial pathology. A rationale for
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